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OBJECTIVE: This study investigated inter-rater agreement (IRA) among EEG experts for the identification of electrographic seizures and periodic discharges (PDs) in continuous ICU EEG recordings. METHODS: Eight board-certified EEG experts independently identified seizures and PDs in thirty 1-h EEG segments which were selected from ICU EEG recordings collected from three medical centers. IRA was compared between seizure and PD identifications, as well as among rater groups that have passed an ICU EEG Certification Test, developed by the Critical Care EEG Monitoring Research Consortium (CCEMRC). RESULTS: Both kappa and event-based IRA statistics showed higher mean values in identification of seizures compared to PDs (k=0.58 vs. 0.38; p<0.001). The group of rater pairs who had both passed the ICU EEG Certification Test had a significantly higher mean IRA in comparison to rater pairs in which neither had passed the test. CONCLUSIONS: IRA among experts is significantly higher for identification of electrographic seizures compared to PDs. Additional instruction, such as the training module and certification test developed by the CCEMRC, could enhance this IRA. SIGNIFICANCE: This study demonstrates more disagreement in the labeling of PDs in comparison to seizures. This may be improved by education about standard EEG nomenclature.

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AIM: To compare the prevalence of psychopathology in infants born preterm with matched full-term infants at the corrected age of 1 year. METHODS: Between June 2003 and April 2005, a case-control longitudinal cohort study was conducted at the neonatal unit of the University Hospital of Antwerp, Belgium. We prospectively enrolled 123 live-born infants between 25 and 35 weeks of gestation and/or infants with a birth-weight of <1500 g. Thirty full-term infants were recruited among day care centres in the region. Diagnoses were based on the Diagnostic Classification Zero to Three (DC: 0-3), using the MacArthur Communicative Developmental Inventory Dutch version, Infant-Toddler Sensory Profile, Bayley Scales of Infant Development II, Parent Infant Relationship Global Assessment Scale and Functional Emotional Assessment Scale. RESULTS: At the (corrected) age of 12 months, 89 infants were eligible for follow-up and complete data were available for 69 (77%) infants. Fifty-four percentage of the preterm infants fulfilled one or more DC 0-3 diagnoses. Premature infants had significantly more diagnoses than full-term infants on axis I, axis III and axis V of the DC: 0-3. CONCLUSION: In this study, the prevalence of psychopathology was significantly higher among preterm infants in comparison with full-term infants. This study did not confirm previous findings of higher rates of relationship disorders among preterm infants.

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OBJECTIVE: To develop an easy-to-use bedside scoring system, composed of clinical variables, hematologic variables, and risk factors of infection, to predict nosocomial sepsis in neonatal intensive care unit patients. SETTING: A neonatal intensive care unit in a university hospital, Antwerp, Belgium. PATIENTS: Over 2 yrs, we analyzed two groups of patients. First, we prospectively studied 104 episodes of presumed nosocomial sepsis in 80 neonates (derivation cohort), and then we retrospectively studied 50 episodes in 39 neonates (validation cohort). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed two versions of a scoring system to predict nosocomial sepsis in sick neonates. The first scoring system (NOSEP-1 score) was based on 15 clinical, 12 laboratory, and 17 historical variables potentially connected with infection; the second one (NOSEP-2 score) also included the culture results of central vascular catheters. Based on the odds ratios of all independent variables, an additive and weighted score was developed and validated in a cohort of 39 patients screened for nosocomial sepsis in the same center. The NOSEP-1 score consisted of three laboratory variables (C-reactive protein > or =14 mg/L, thrombocytopenia <150 x 10(9)/L, and neutrophil fraction >50%), one clinical factor (fever >38.2 degrees C [100.8 degrees F]), and one risk factor (parenteral nutrition for > or =14 days). The NOSEP-2 score consisted of the same variables plus catheter-hub and catheter insertion site colonization data. Receiver operating characteristic curve analysis demonstrated good predictor performance of the NOSEP-1 score (area under the curve [Az] = 0.82 +/- 0.04 [SEM]) and NOSEP-2 score (Az = 0.84 +/- 0.04, p < .05). We checked whether a complex computer-generated scoring system (CD-1 and CD-2 scores) based on the original numerical values of the items used in NOSEP-1 and NOSEP-2 would improve the prediction of nosocomial sepsis. The analysis showed the accuracy of bedside NOSEP-1 and NOSEP-2 scores to be comparable with the more cumbersome computer-generated CD-1 and CD-2 scores (receiver operating characteristic curve, Az: CD-1 score = 0.81 +/- 0.04, p = .69, and CD-2 score = 0.86 +/- 0.04, p = .96). Finally, in the validation cohort, we showed that the developed scoring system has a good prediction potential for nosocomial sepsis (Hosmer-Lemeshow goodness-of-fit test, chi2 [19] = 16.34, p > .75). CONCLUSIONS: The simple bedside scoring system NOSEP-1 composed of C-reactive protein, neutrophil fraction, thrombocytopenia, fever, and prolonged parenteral nutrition exposure provides a valuable tool for early identification of nosocomial sepsis. Its predictive power can be improved by adding central vascular catheter insertion site and hub colonization to the score.

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OBJECTIVE: To obtain data on the ontogeny of catecholamines and other chromaffin vesicle components, which could serve as a basis for the study of their role during fetal life in normal and pathologic conditions. DESIGN: Epinephrine, norepinephrine, dopamine-beta-hydroxylase, and chromogranin A contents were measured in the porcine adrenal gland during various stages of gestation. ANIMALS: 934 porcine fetuses representing 22 gestational ages between 43 and 108 days. PROCEDURE: Total homogenates of adrenal glands were extracted and contents of different neurochemical markers were measured, using high-performance liquid chromatography, immunoassays, and western blotting. Immunohistochemical studies also were performed. RESULTS: Epinephrine and norepinephrine contents as a function of gestational age can be represented by a sigmoidal curve. Norepinephrine content rises early in gestation, whereas epinephrine content increases later. Maximal increase was significantly higher for epinephrine content. A progressive appearance of separate epinephrine- and norepinephrine-storing cells was documented. Dopamine-beta-hydroxylase content as a function of gestational age can be adequately represented by a parabolic curve. No quantitative changes in chromogranin A concentration were observed, but western blotting revealed qualitative changes with progressing gestational age. CONCLUSIONS: Important changes occur in catecholamine formation around day 60 of gestation. The sharp increase in epinephrine/norepinephrine contents and the appearance of separate epinephrine- and norepinephrine-storing cells may be related to the progressive splanchnic innervation of the adrenal gland. The presence of chromogranin A early in gestation may indicate its necessity for catecholamine storage.

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Mac-1 and LFA-1, members of the leukocyte or CD18 integrin subfamily of adhesion molecules, rapidly change from a low avidity to a high avidity state on activation of neutrophils by various agonists. The control of CD18 integrin-dependent neutrophil adhesion and the mechanisms that regulate integrin avidity are poorly understood. Cytoplasmic domain deletion experiments indicate that the cytoplasmic domains of integrins are necessary for proper integrin function and suggest that interactions with intracellular proteins are involved. We have focused on identifying cytoskeletal proteins that interact with the cytoplasmic domain of the beta-subunit (beta 2 or CD18) common to the leukocyte subfamily of integrins, which include LFA-1, Mac-1, and p150,95. The actin binding protein alpha-actinin associates in vitro with a peptide corresponding to a portion of the CD18 cytoplasmic domain in solid phase binding assays and affinity chromatography experiments. The peptide sequence within the CD18 cytoplasmic domain that binds alpha-actinin is homologous with a region in the cytoplasmic domain of the integrin beta 1-subunit, which also binds alpha-actinin. We demonstrate that the association of alpha-actinin with CD18 is physiologically relevant by coimmunoprecipitating CD18 with alpha-actinin from stimulated human neutrophils under nondenaturing conditions. Using a mAb against CD18 to probe Western blots of immunoprecipitated complexes, CD18 was found to coprecipitate with alpha-actinin when cells were activated with the chemotactic peptide FMLP or with the cytokines leukotriene B4 or TNF-alpha. Very little CD18 coprecipitates with alpha-actinin from unactivated cells. FMLP concentrations as low as 10 nM were sufficient to induce the association of CD18 with alpha-actinin; very little association was detected in cells activated with 1 nM FMLP. The association between alpha-actinin and CD18 was transient, peaking 5-10 min after activation and decreasing to near resting levels by 20 min. CD18 did not coimmunoprecipitate with talin or vinculin in vivo. We conclude that activation of neutrophils results in an alpha-actinin-mediated association between CD18 integrins and actin filaments. In addition to its actin bundling activity, alpha-actinin has a major function as an actin membrane linker molecule, and integrin avidity may be affected by an association with the actin cytoskeleton involving alpha-actinin.

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